Deciphering the """"""""conversation"""""""" between bacterium and host during infection is central to understanding microbial pathogenesis and host defense. Periodontal diseases have long been recognized as bacterial infections, and a long-term goal of the laboratory is to identify P. gingivalis genes expressed during infection, ie. one side of the cross-talk between bacterium and host. The genetic tractability of the organism, combined with the availability of a completed genome sequence and gene microarrays, has made this goal approachable. Bacteria use two-component signal transduction systems to monitor and react to changes in their environment. In this application, we test the hypothesis that in P. gingivalis these systems are responsive to in vivo conditions prevailing in the subgingival crevice during health and disease. A comprehensive study is proposed of the molecular mechanisms of gene regulation in P. gingivalis, a new area of research with this organism. Response regulators will be analyzed to identify the genes they control, and their promoter targets. We will test our hypothesis by determining the expression of a subset of identified genes in the in vivo environment of subgingival plaque from periodontitis patients. The experimental approaches exploit our experience in molecular genetics, whole genome transcription profiling, promoter target localization, and DNA sequence analysis. The goals are responsive to the RFA since we will analyze P. gingivalis intracellular signaling mechanisms that orchestrate responses to environmental changes. By defining the regulators, the genes they control, and their in vitro and in vivo expression patterns, we can identify conditions that may trigger periodontitis, and target rational therapeutic interventions to the regulatory molecular switches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE015931-01
Application #
6795202
Study Section
Special Emphasis Panel (ZDE1-YL (16))
Program Officer
Mangan, Dennis F
Project Start
2004-04-01
Project End
2007-12-31
Budget Start
2004-04-01
Budget End
2004-12-31
Support Year
1
Fiscal Year
2004
Total Cost
$536,792
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
062190616
City
Cambridge
State
MA
Country
United States
Zip Code
02142
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Krishnan, Karthik; Duncan, Margaret J (2013) Role of sodium in the RprY-dependent stress response in Porphyromonas gingivalis. PLoS One 8:e63180
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Nishikawa, Kiyoshi; Duncan, Margaret J (2010) Histidine kinase-mediated production and autoassembly of Porphyromonas gingivalis fimbriae. J Bacteriol 192:1975-87
Chen, Weilin; Kajiya, Mikihito; Giro, Gabriela et al. (2010) Bacteria-derived hydrogen sulfide promotes IL-8 production from epithelial cells. Biochem Biophys Res Commun 391:645-50
Duran-Pinedo, Ana E; Nishikawa, Kiyoshi; Duncan, Margaret J (2007) The RprY response regulator of Porphyromonas gingivalis. Mol Microbiol 64:1061-74